Abstract 2218: Genomic characterisation of 1015 cancer cell-lines

Abstract

Abstract Over the last twenty years there has been a paradigm shift in cancer treatment, moving away from the cytotoxic effects of chemicals targeting all cells going through cell division to a more targeted approach aimed at inactivating specific cellular components upon which the cancers rely to drive cell growth, a process termed oncogene addiction. The ‘poster child’ for such therapies is ‘imatinib' a small molecule inhibitor of ABL kinase activity targeting the BCR-ABL fusion protein in CML. We present the genomic characterisation of 1015 cancer cell lines currently being used as reagents in a high-throughput screen of anti-cancer agents. Future analysis combining these genomic and drug resistance data will aid in identifying the underlying genetics of drug sensitivity and allow for identification of biomarkers with which to stratify patients, identifying those most likely to respond to specific cancer therapies. To characterise the cell lines we performed exome sequencing and copy number analysis. Since most cell lines are unmatched we screened out germline variants by comparison to ∼8000 normal exomes, giving a set of ∼500,000 putative somatic non-synonymous variants. To reduce the ‘genetic space’ for the subsequent downstream correlation to drug response data we further filtered the variants to identify those most likely to have a functional effect or contribute to carcinogenesis. Two such filters were applied, the ‘Functional Analysis through Hidden Markov Models’ (FATHMM) algorithm and a series of checks identifying recurrence of variants in the ‘systematic screening data' held in the COSMIC database. Application of these filters reduced the number of variants to be taken forward to ∼115,000 and 30,000 respectively. The variant data for the cancer cell lines is available via the COSMIC web portal. Citation Format: Graham R. Bignell, Francesco Iorio, Andrew Futreal, Michael R. Stratton, Peter Campbell, Ultan McDermott. Genomic characterisation of 1015 cancer cell-lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2218. doi:10.1158/1538-7445.AM2014-2218